ART Program of the HIV Vaccine Trials Network Margaret Wecker, PhD Associate Director, Scientific Operations and Business Development

HVTN Organization HVTN functions under a cooperative agreement with the US National Institutes of Health The Division of AIDS (DAIDS) is within the National Institute for Allergy and Infectious Disease HVTN established in 2000 and has been awarded a second 7-year grant cycle, starting in 2007 Network of research institutions 14 domestic sites, and 14 international sites on 5 continents

HVTN Clinical Research Sites

HVTN Sites DomesticInternational AtlantaRioChang Mai BirminghamSao PauloCape Town BostonLimaDurban ChicagoIquitosKlerksdorp NashvillePort-au-PrincePretoria New York CitySan JuanSoweto PhiladelphiaDRLausanne RochesterKingston Seattle San Francisco Raleigh

Provision of Treatment in HIV-1 Vaccine Trials in Developing Countries. (The Lancet, September, 2003) The HIV Vaccine Trials Network (HVTN), a collaboration of scientists from 28 research sites (figure), announced this year that participants who become infected during HVTN vaccine trials will receive long-term antiretroviral treatment.

Challenges to Fulfilling our Promise Funding –NIH grant will not support purchase of ART –Mandate is to perform HIV vaccine research –Cannot support monitoring or testing outside a clinical trial 7-year grant cycle…. But a lifetime commitment? Start of treatment may be years after completion of clinical trial

Funding and Prioritization A separate fund was established – Seattle Vaccine Research Fund Vaccine developers asked to donate to this fund to support provision of ART to participants in HVTN HIV vaccine trials With limited funds available, prioritization is necessary –Goal is to ensure that volunteers who become HIV infected during the course of a HVTN HIV vaccine trial have access to ART when they meet local treatment guidelines until a national plan is in place –Fund of “last resort”

Limitations of the program Limited to HVTN Sites in countries outside the US without government plan for ART Unable to provide support for monitoring the participant outside the context of a clinical trial –HVTN does have several follow-up trials offered to HIV- infected trial participants including one trial in which participants receive ART Unable to provide support for partners or immediate family Unable to provide support for concurrent STIs, OIs etc.

HVTN ART Program Purchase of ART CD4, Viral load and safety monitoring associated with ART Individual sites have ownership of ART plans –HVTN Core works with sites to prepare country-specific ART Plans –Provide information for treatment cost estimates –Identify gaps in funding for ppts –Revised as necessary consistent with status of national plans

Processes PPT becomes HIV infected during HVTN vaccine trial –Issued ID Card and Brochure –Is tracked in HVTN database and a serial number is provided for ART fund tracking Application for funding –Serial number or ppt identifier –Treatment proposal Funds transferred to allow provision of ART

Responsibilities SVRF –Maintain database –Evaluate requests –Disburse funds to RPIC –Receive reports of fund disbursement and program termination RPIC (The fiduciary) –Applies for funding –Report of fund disbursement  purchase of medication for given participant – Report termination of program  death  national plan status change

To Date < 2% of Participants Have Become HIV-Infected As of September, 2007: 79 HIV-infected participants, out of a total of 5764 enrollees. Infections from:Number of infections Phase I-II protocols22 HVTN HVTN 903 (a vaccine preparedness trial, not eligible) 10 non eligible countries (including US)45 Infections from eligible countries and studies24

Future Challenges Implementation Sustainability Shifting need pattern from developing world to developed world?